Patient-Specific Factors Predicting Renal Denervation Response in Patients With Hypertension: A Systematic Review and Meta-Analysis.

BACKGROUND: The accurate selection of patients likely to respond to renal denervation (RDN) is crucial for optimizing treatment outcomes in patients with hypertension. This systematic review was designed to evaluate patient-specific factors predicting the RDN response. METHODS AND RESULTS: We focused on individuals with hypertension who underwent RDN. Patients were categorized based on their baseline characteristics. The primary outcome was blood pressure (BP) reduction after RDN. Both randomized controlled trials and nonrandomized studies were included. We assessed the risk of bias using corresponding tools and further employed the Grading of Recommendations Assessment, Development, and Evaluation approach to assess the overall quality of evidence. A total of 50 studies were ultimately included in this systematic review, among which 17 studies were for meta-analysis. Higher baseline heart rate and lower pulse wave velocity were shown to be associated with significant antihypertensive efficacy of RDN on 24-hour systolic BP reduction (weighted mean difference, -4.05 [95% CI, -7.33 to -0.77]; weighted mean difference, -7.20 [95% CI, -9.79 to -4.62], respectively). In addition, based on qualitative analysis, higher baseline BP, orthostatic hypertension, impaired baroreflex sensitivity, and several biomarkers are also reported to be associated with significant BP reduction after RDN. CONCLUSIONS: In patients with hypertension treated with the RDN, higher heart rate, and lower pulse wave velocity were associated with significant BP reduction after RDN. Other factors, including higher baseline BP, hypertensive patients with orthostatic hypertension, BP variability, impaired cardiac baroreflex sensitivity, and some biomarkers are also reported to be associated with a better BP response to RDN.

Heterogeneous body compositions and all-cause mortality in acute coronary syndrome patients: a ten-year retrospective cohort study.

BACKGROUND: The association of different body components, including lean mass and body fat, with the risk of death in acute coronary syndrome (ACS) patients are unclear. METHODS: We enrolled adults diagnosed with ACS at our center between January 2011 and December 2012 and obtained follow-up outcomes via telephone questionnaires. We used restricted cubic splines (RCS) with the Cox proportional hazards model to analyze the associations between body mass index (BMI), predicted lean mass index (LMI), predicted body fat percentage (BF), and the value of LMI/BF with 10-year mortality. We also examined the secondary outcome of death during hospitalization. RESULTS: During the maximum 10-year follow-up of 1398 patients, 331 deaths (23.6%) occurred, and a U-shaped relationship was found between BMI and death risk (P nonlinearity = 0.03). After adjusting for age and history of diabetes, the overweight group (24 ≤ BMI < 28 kg/m2) had the lowest mortality (HR = 0.53, 95% CI: 0.29-0.99). Predicted LMI and LMI/BF had an inverse linear relationship with a 10-year death risk (P nonlinearity = 0.24 and P nonlinearity = 0.38, respectively), while an increase in BF was associated with increased mortality (P nonlinearity = 0.64). During hospitalization, 31 deaths (2.2%) were recorded, and the associations of the indicators with in-hospital mortality were consistent with the long-term outcome analyses. CONCLUSION: Our study provides new insight into the "obesity paradox" in ACS patients, highlighting the importance of considering body composition heterogeneity. Predicted LMI and BF may serve as useful tools for assessing nutritional status and predicting the prognosis of ACS, based on their linear associations with all-cause mortality.

The management of non-culprit vessel(s) in patients with unstable angina/non-ST elevation myocardial infarction and chronic kidney dysfunction.

BACKGROUND AND AIMS: The clinical effects of multivessel interventions in patients with unstable angina/non-ST-segment elevation myocardial infarction (UA/NSTEMI), multivessel disease (MVD) and chronic kidney disease (CKD) remain uncertain. This study aimed to investigate the safety and effectiveness of intervention in non-culprit lession(s) among this cohort. METHODS: We consecutively included patients diagnosed with UA/NSTEMI, MVD and CKD between January 2008 and December 2018 at our centre. After successful percutaneous coronary intervention (PCI), we compared 48-month overall mortality between those undergoing multivessel PCI (MV-PCI) through a single-procedure or staged-procedure approach and culprit vessel-only PCI (CV-PCI) after 1:1 propensity score matching. We conducted stratified analyses and tests for interaction to investigate the modifying effects of critical covariates. Additionally, we recorded the incidence of contrast-induced nephropathy (CIN) to assess the perioperative safety of the two treatment strategies. RESULTS: Of the 749 eligible patients, 271 pairs were successfully matched. Those undergoing MV-PCI had reduced all-cause mortality (hazard ratio (HR): 0.67, 95% confidence interval (CI): 0.48-0.67). Subgroup analysis showed that those with advanced CKD (estimated glomerular filtration rate (eGFR) ≤ 30 mL/min/1.73 m2 ) could not benefit from MV-PCI (P = 0.250), and the survival advantage also tended to diminish in diabetes (P interaction < 0.01; HR = 0.95, 95% CI = 0.65-1.45). Although the staged-procedure approach (N = 157) failed to bring additional survival benefits compared to single-procedure MV-PCI (N = 290) (P = 0.460), it showed a tendency to decrease the death risk. CIN risks in MV-PCI and CV-PCI groups were not significantly different (risk ratio = 1.60, 95% CI = 0.94-2.73). CONCLUSION: Among patients with UA/NSTEMI and non-diabetic CKD and an eGFR > 30 mL/min/1.73 m2 , MV-PCI was associated with a reduced risk of long-term death but did not increase the incidence of CIN during the management of MVD compared to CV-PCI. And staged procedures might be a preferable option over single-procedure MV-PCI.

His-Purkinje conduction system pacing combined with atrioventricular node ablation improves quality of life in older patients with persistent atrial fibrillation refractory to multiple ablation procedures.

BACKGROUND: Recurrence of atrial fibrillation (AF) is common in patients with persistent AF even after multiple ablation procedures. His-Purkinje conduction system pacing (HPCSP) combined with atrioventricular node ablation (AVNA) is effective in managing patients with AF and heart failure. This study aimed to determine whether HPCSP combined with AVNA can improve quality of life and alleviate symptoms in older patients with symptomatic persistent AF refractory to multiple ablation procedures, as well as evaluate the feasibility and safety of this therapy. METHODS: Older patients (≥ 65 years) with symptomatic persistent AF refractory to at least two ablation procedures were treated with combined HPCSP and AVNA. The success rates and complications were recorded. Pacing parameters, European Heart Rhythm Association (EHRA) scores, and Atrial Fibrillation Effect on Quality-of-Life (AFEQT) scores obtained perioperatively were compared with those recorded at the 6-month follow-up examination. RESULTS: Thirty-one patients were enrolled; of those, only thirty patients were eventually treated with AVNA because one patient developed a complete atrioventricular block following the withdrawal of the His bundle pacing lead. The success rates were 100% for HPCSP (22 cases with His bundle pacing, and 9 cases with left bundle branch pacing) and 93.3% (28/30) for AVNA, respectively. By the 6-month follow-up examination, EHRA scores improved significantly (3.00 ± 0.73 vs. 2.44 ± 0.63, P = 0.014) and AFEQT scores increased markedly (49.6 ± 20.6 vs. 70.9 ± 14.0, P = 0.001). No severe complications developed. CONCLUSIONS: When used in older patients with symptomatic persistent AF refractory to multiple ablation procedures, HPCSP combined with AVNA significantly alleviated symptoms and improved quality of life during short-term follow-up. This therapy was proved to be safe and effective in this patient population.

Gut microbiota mediates the pharmacokinetics of Zhi-zi-chi decoction for the personalized treatment of depression.

ETHNOPHARMACOLOGICAL RELEVANCE: Zhi-zi-chi decoction (ZZCD), from "Treatise on Febrile Diseases", is a typical traditional Chinese medicine herb pair, which consists of Gardeniae Fructus (GF) and Semen Sojae Praeparatu (SSP). In clinical research, ZZCD was widely used to fight depression, remove annoyance. Many studies have reported that gut microbiota is critical target for the influence of depress through gut-brain axis, and our previously studies have found that ZZCD exhibiting antidepressant effect was through the gut-brain axis. However, the specific mechanism by which gut microbiota mediates the pharmacokinetics parameters of active compounds from ZZCD during the process of depression treatment has not yet been studied. AIM OF THE STUDY: To explore the differences in pharmacokinetics characters of bioactive iridoids from ZZCD and study the changes of gut microbiota at different stages of depression with the personalized medicine of ZZCD. MATERIALS AND METHODS: A new strategy exploring the relationship among disease phenotypes (D), intestinal microbiota (I), enzymes (E) and traits of metabolism (T) named as "DIET" was established. Firstly, a fast, selective and sensitive ultra-performance liquid chromatography coupled with tandem mass spectrometer (UPLC-MS/MS) was established and validated to quality the main bioactive compounds from ZZCD and compare the pharmacokinetics and bioavailability of different iridoids prototypes and metabolites from ZZCD between normal and chronic unpredictable mild stress rats. Subsequently, the activity of corresponding metabolic enzymes of anti-depressive compounds, ß-glucosidases and sulfotransferases, were analyzed by ρ-nitrophenyl-ß -D-glucopyranoside and sulfotransferases ELISA kits, respectively. Finally, 16S rRNA gene sequencing was adopt to analyze intestinal bacteria composition for the treatment of depression by ZZCD. RESULTS: The antidepressant effect of ZZCD was promoted due to the increased exposures and reduced eliminations of anti-depressive compounds, especially geniposide and genipin 1-gentiobioside, under the depression state. With the ZZCD treatment, the depression was improved, but the exposures of anti-depressive compounds from ZZCD gradually decreased. Meanwhile, there were the corresponding decreased trends on the activity of ß-glucosidases and sulfotransferases. With the consumption of ZZDC and the improvement of depression, the exposures of anti-depressive iridoid glycosides decreased and the activity of metabolism enzymes restored. Meanwhile, the dysbiosis of pathogenic bacteria (Bacteroidota) induced by depression was ameliorated and the probiotics (Firmicutes) at the phylum and genus level raised, the two phyla are closely related to the production of ß-glucosidase and sulfotransferases. CONCLUSIONS: It is the first proposed that ZZCD could personalized to treat depression at different stages targeting gut microbiota and gut microbiome could emerged as a potential diagnostic and therapeutic biomarker in depression.

Performance of the Risk Scores for Predicting In-Hospital Mortality in Patients with Acute Coronary Syndrome in a Chinese Cohort.

Background: The prognosis of patients with acute coronary syndrome (ACS) varies greatly, and risk assessment models can help clinicians to identify and manage high-risk patients. While the Global Registry of Acute Coronary Events (GRACE) model is widely used, the clinical pathways for acute coronary syndromes (CPACS), which was constructed based on the Chinese population, and acute coronary treatment and intervention outcomes network (ACTION) have not yet been validated in the Chinese population. Methods: Patients with ACS who underwent coronary angiography or percutaneous coronary intervention from 2011 to 2020, were retrospectively recruited and the appropriate corresponding clinical indicators was obtained. The primary endpoint was in-hospital mortality. The performance of the GRACE, GRACE 2.0, ACTION, thrombolysis in myocardial infarction (TIMI) and CPACS risk models was evaluated and compared. Results: A total of 19,237 patients with ACS were included. Overall, in-hospital mortality was 2.2%. ACTION showed the highest accuracy in predicting discriminated risk (c-index 0.945, 95% confidence interval [CI] 0.922-0.955), but the calibration was not satisfactory. GRACE and GRACE 2.0 did not significantly differ in discrimination (p = 0.1480). GRACE showed the most accurate calibration in all patients and in the subgroup analysis of all models. CPACS (c-index 0.841, 95% CI 0.821-0.861) and TIMI (c-index 0.811, 95% CI 0.787-0.835) did not outperform (c-index 0.926, 95% CI 0.911-0.940). Conclusions: In contemporary Chinese ACS patients, the ACTION risk model's calibration is not satisfactory, although outperformed the gold standard GRACE model in predicting hospital mortality. The CPACS model developed for Chinese patients did not show better predictive performance than the GRACE model.

Total Arterial Revascularization in Diabetic Patients Undergoing Coronary Artery Bypass Graft Surgery: A Systematic Review and Meta-Analysis.

Background: Total arterial revascularization (TAR) has gradually become accepted and recognized, but its effect and safety in diabetic patients are not clear. We performed a systematic review and meta-analysis to summarize the safety and efficacy of TAR and additionally evaluated the clinical outcomes of arterial revascularization using different arterial deployments in patients with diabetes. Methods: PubMed, Embase, and the Cochrane Library databases from inception to July 2022 for studies that studied the effect of arterial revascularization in diabetic patients undergoing isolated coronary artery bypass graft (CABG) were searched. The primary outcome was long-term ( ≥ 12 months of follow-up) death by any cause. The secondary efficacy endpoints were long-term ( ≥ 12 months) cardiovascular death, early sternal wound infection (SWI) and death ( ≤ 30 days or in hospital). Risk ratios (RRs), hazard ratios (HRs), and their corresponding 95% confidence intervals (CIs) were calculated to describe short-term results and long-term survival outcomes. Two different ways were used to analyze the effect of TAR and the impact of diabetes on the clinical outcomes of TAR. Results: Thirty-five studies were included in the study, covering 178,274 diabetic patients. Compared to conventional surgery with saphenous veins, TAR was not associated with increased early mortality (RR 0.77, 95% CI 0.48-1.23) and risk of SWI (RR 0.77, 95% CI 0.46-1.28). The overall Kaplan-Meier survival curves based on reconstructed patient data indicated a significant association between TAR and reduced late mortality (HR 0.52, 95% CI 0.48-0.67) and the curves based on the propensity-score matched (PSM) analyses suggested a similar result (HR 0.74, 95% CI 0.66-0.85). TAR could also effectively decrease the risk of cardiovascular death (HR 0.42, 95% CI 0.24-0.75). Through comparing the effect of TAR in patients with and without diabetes, we found that the presence of diabetes did not elevate the risk of early adverse events (death: RR 1.50, 95% CI 0.64-3.49; SWI: RR 2.52, 95% CI 0.91-7.00). Although diabetes increased long-term mortality (HR 1.06; 95% CI 1.35-2.03), the cardiovascular death rate was similar in patients with diabetes and patients without diabetes (HR 1.09; 95% CI 0.49-2.45). Regarding the selection of arterial conduits, grafting via the bilateral internal mammary artery (BIMA) decreased the risk of overall death (HR 0.67, 95% CI 0.52-0.85) and cardiovascular death (HR 0.55, 95% CI 0.35-0.87) without resulting in a significantly elevated rate of early death (RR 0.95, 95% CI 0.82-1.11). However, the evidence from PSM studies indicated no difference between the long-term mortality of the BIMA group and that of the single internal mammary arteries (SIMA) groups (HR 0.76, 95% CI 0.52-1.11), and the risk of SWI was significantly increased by BIMA in diabetes (RR 1.65, 95% CI 1.42-1.91). The sub-analysis indicated the consistent benefit of the radial artery (RA) application in diabetic patients (HR 0.71, 95% CI 0.63-0.79) compared to saphenous vein graft. In two propensity-score-matched studies, the evidence showed that the survival outcomes of the BIMA group were similar to that of the SIMA plus RA group but that grafting via the RA reduced the risk of sternal wound infection. Conclusions: Compared with conventional surgery using SVG, TAR was associated with an enhanced survival benefit in diabetes and this long-term gain did not increase the risk of early mortality or SWI. Given the increased infection risk and controversial long-term survival gains of grafting via the BIMA in diabetes, its wide use for grafting in this cohort should be seriously considered. Compared to using the right internal mammary artery (RIMA), RA might be a similarly effective but safer option for patients with diabetes.

5-Methyl-cytosine stabilizes DNA but hinders DNA hybridization revealed by magnetic tweezers and simulations.

5-Methyl-cytosine (5mC) is one of the most important DNA modifications and plays versatile biological roles. It is well known that 5mC stabilizes DNA duplexes. However, it remains unclear how 5mC affects the kinetics of DNA melting and hybridization. Here, we studied the kinetics of unzipping and rezipping using a 502-bp DNA hairpin by single-molecule magnetic tweezers. Under constant loading rates, 5mC increases the unzipping force but counterintuitively decreases the rezipping force at various salt and temperature conditions. Under constant forces, the non-methylated DNA hops between metastable states during unzipping and rezipping, which implies low energy barriers. Surprisingly, the 5mC DNA can't rezip after fully unzipping unless much lower forces are applied, where it rezips stochastically in a one-step manner, which implies 5mC kinetically hinders DNA hybridization and high energy barriers in DNA hybridization. All-atom molecular dynamics simulations reveal that the 5mC kinetically hinders DNA hybridization due to steric effects rather than electrostatic effects caused by the additional methyl groups of cytosines. Considering the possible high speed of DNA unzipping and zipping during replication and transcription, our findings provide new insights into the biological roles of 5mC.

Secondary damage and neuroinflammation in the spinal dorsal horn mediate post-thalamic hemorrhagic stroke pain hypersensitivity: SDF1-CXCR4 signaling mediation.

Central post-stroke pain (CPSP) is an intractable neuropathic pain, which can be caused by primary lesion of central somatosensory system. It is also a common sequelae of the thalamic hemorrhagic stroke (THS). So far, the underlying mechanisms of CPSP remain largely unknown. Our previous studies have demonstrated that SDF1-CXCR4 signaling in the hemorrhagic region contributes to the maintenance of the THS pain hypersensitivity via mediation of the thalamic neuroinflammation. But whether the spinal dorsal horn, an initial point of spinothalamic tract (STT), suffers from retrograde axonal degeneration from the THS region is still unknown. In this study, neuronal degeneration and loss in the spinal dorsal horn were detected 7 days after the THS caused by intra-thalamic collagenase (ITC) injection by immunohistochemistry, TUNEL staining, electron microscopy, and extracellular multi-electrode array (MEA) recordings, suggesting the occurrence of secondary apoptosis and death of the STT projecting neuronal cell bodies following primary THS via retrograde axonal degeneration. This retrograde degeneration was accompanied by secondary neuroinflammation characterized by an activation of microglial and astrocytic cells and upregulation of SDF1-CXCR4 signaling in the spinal dorsal horn. As a consequence, central sensitization was detected by extracellular MEA recordings of the spinal dorsal horn neurons, characterized by hyperexcitability of both wide dynamic range and nociceptive specific neurons to suprathreshold mechanical stimuli. Finally, it was shown that suppression of spinal neuroinflammation by intrathecal administration of inhibitors of microglia (minocycline) and astrocytes (fluorocitrate) and antagonist of CXCR4 (AMD3100) could block the increase in expression levels of Iba-1, GFAP, SDF1, and CXCR4 proteins in the dorsal spinal cord and ameliorate the THS-induced bilateral mechanical pain hypersensitivity, implicating that, besides the primary damage at the thalamus, spinal secondary damage and neuroinflammation also play the important roles in maintaining the central post-THS pain hypersensitivity. In conclusion, secondary neuronal death and neuroinflammation in the spinal dorsal horn can be induced by primary thalamic neural damage via retrograde axonal degeneration process. SDF1-CXCR4 signaling is involved in the mediation of secondary spinal neuroinflammation and THS pain hypersensitivity. This finding would provide a new therapeutic target for treatment of CPSP at the spinal level.

Inhibitions and Down-Regulation of Motor Protein Eg5 Expression in Primary Sensory Neurons Reveal a Novel Therapeutic Target for Pathological Pain.

The motor protein Eg5, known as kif11 or kinesin-5, interacts with adjacent microtubules in the mitotic spindle and plays essential roles in cell division, yet the function of Eg5 in mature postmitotic neurons remains largely unknown. In this study, we investigated the contribution and molecular mechanism of Eg5 in pathological pain. Pharmacological inhibition of Eg5 and a specific shRNA-expressing viral vector reversed complete Freund's adjuvant (CFA)-induced pain and abrogated vanilloid receptor subtype 1 (VR1) expression in dorsal root ganglion (DRG) neurons. In the dorsal root, Eg5 inhibition promoted VR1 axonal transport and decreased VR1 expression. In the spinal cord, Eg5 inhibition suppressed VR1 expression in axon terminals and impaired synapse formation in superficial laminae I/II. Finally, we showed that Eg5 is necessary for PI3K/Akt signalling-mediated VR1 membrane trafficking and pathological pain. The present study provides compelling evidence of a noncanonical function of Eg5 in primary sensory neurons. These results suggest that Eg5 may be a potential therapeutic target for intractable pain.

A Temporal Activity of CA1 Neurons Underlying Short-Term Memory for Social Recognition Altered in PTEN Mouse Models of Autism Spectrum Disorder.

Memory-guided social recognition identifies someone from previous encounters or experiences, but the mechanisms of social memory remain unclear. Here, we find that a short-term memory from experiencing a stranger mouse lasting under 30 min interval is essential for subsequent social recognition in mice, but that interval prolonged to hours by replacing the stranger mouse with a familiar littermate. Optogenetic silencing of dorsal CA1 neuronal activity during trials or inter-trial intervals disrupted short-term memory-guided social recognition, without affecting the ability of being sociable or long-term memory-guided social recognition. Postnatal knockdown or knockout of autism spectrum disorder (ASD)-associated phosphatase and tensin homolog (PTEN) gene in dorsal hippocampal CA1 similarly impaired neuronal firing rate in vitro and altered firing pattern during social recognition. These PTEN mice showed deficits in social recognition with stranger mouse rather than littermate and exhibited impairment in T-maze spontaneous alternation task for testing short-term spatial memory. Thus, we suggest that a temporal activity of dorsal CA1 neurons may underlie formation of short-term memory to be critical for organizing subsequent social recognition but that is possibly disrupted in ASD.

Proteomic analysis of individual giant freshwater prawn, Macrobrachium rosenbergii, growth retardants.

"Iron prawn" is a condition of severe growth retardation that fishers call. The giant river prawn (Macrobrachium rosenbergii) is a commercially important species contains high protein content and functional nutrients. However, no proteomic information is available for this species. We performed the shotgun 2DLC-MS/MS proteomic analysis of the total protein from "iron prawn". Total 19,758 peptides corresponding to 2613 high-confidence proteins were identified. These proteins range in size from 40 to 70 kDa. KEGG analysis revealed that the largest group consisting total 102 KEGG pathway proteins comparing the "iron prawn" with the normal prawn. Additionally, 7, 11, 1, 6, and 5 commercially important enzymes were found in the eyestalk, liver, muscle, ovary, and testis, respectively. The functions of these differently expressed enzymes include immune system action against pathogens, muscle contraction, digestive system metabolism, cell differentiation, migration, and apoptosis in the severe growth retardation of "iron prawn". Our work provides insight into the understanding of the formation mechanism of "iron prawn".

Wavelet Element Modelling for Inviscid Fluid-Solid Coupling Problem based on Partitioned Approach.

To provide a simple numerical formulation based on fixed grids, a wavelet element method for fluid-solid modelling is introduced in this work. Compared with the classical wavelet finite element method, the presented method can potentially handle more complex shapes. Considering the differences between the solid and fluid regions, a damping-like interface based on wavelet elements is designed, in order to ensure consistency between the two parts. The inner regions are constructed with the same wavelet function in space. In the time and spatial domains, a partitioned approach based on Jacobi iteration is combined with the pseudo-parallel calculation method. Numerical convergence analyses show that the method can serve as an alternative choice for fluid-solid coupling modelling.

Cytosine Methylation Enhances DNA Condensation Revealed by Equilibrium Measurements Using Magnetic Tweezers.

CpG methylation of DNA is common in mammalian cells. In sperm, the DNA has the highest level of CpG methylation and is condensed into toroidal structures. How CpG methylation affects DNA structures and interactions is important to understand its biological roles but is largely unknown. Using an RNA-DNA-RNA structure, we observed the equilibrium hopping dynamics between the condensed and extended states of DNA in the presence of polyamines or polylysine peptide as a reduced model of histone tails. Combing with the measured DNA elasticities, we report that CpG methylation of each cytosine nucleotide substantially increases DNA-DNA attraction by up to 0.2 kBT. For the DNA with 57% GC content, the relative increase caused by CpG methylation is up to 32% for the spermine-induced DNA-DNA attraction and up to 9% for the polylysine-induced DNA-DNA attraction. These findings help us to evaluate the energetic contributions of CpG methylation in sperm development and chromatin regulation.

ß-Cell function in obese children and adolescents with metabolic syndrome compared to isolated obesity.

OBJECTIVE: To evaluate ß-cell function in obese children and adolescents meeting clinical criteria for isolated obesity (iOB), isolated components of dysmetabolism (cMD), or metabolic syndrome (MS), and in obese children and adolescents with normal glucose tolerance (NGT), impaired glucose regulation (IGR), or type 2 diabetes (T2DM). STUDY DESIGN: We undertook a prospective study of Han Chinese children and adolescents aged 8-16 years (median 11 ± 1.4) seen in an obesity clinic between May 2013 and 2018. Patients were classified as iOB (53), cMD (139), and MS (139) groups based on clinical criteria. The same patients were also classified as NGT (212), IGR (111), or T2DM (8) based on results of an oral glucose tolerance test (OGTT). The MS patients were classified as NGT [MS](59) and IGR [MS](72) for the further study. All participants also completed a mixed-meal tolerance test (MMTT). RESULTS: Compared with the iOB group, the MS group had significantly higher area under the curve of C-peptide up to the 2 hours (AUC CP) (P = .03) and peak C-peptide (P = .03), adjusted for BMI, age and Tanner stage, on MMTT. However, there was no difference in the insulinogenic index (ΔI30/ΔG30) or oral disposition index (oDI) derived from the OGTT among the three groups. However, 52% of participants with MS had IGR, compared to 28% in the cMD group. Compared with the NGT group, the individuals with IGR had significantly lower ΔI30/ΔG30 (P = .001) and oDI (P < .001). Compared with the iOB group, the NGT[MS] had significantly higher AUC CP (P = .004), peak C-peptide (P = .004) and ΔI30/ΔG30 (P = .007) adjusted for age, but no difference in oDI. Compared with the NGT[MS], the IGR[MS] had significantly lower ΔI30/ΔG30 (P = .005) and oDI (P < .001), but the AUC CP and peak C-peptide had no difference. CONCLUSION: Although the MS youth have ß-cell hyperfunction as a whole, ß-cell dysfunction is present in the early stages of dysmetabolism in obese youth with cMD or MS and worsened across the spectrum from iOB to cMD and MS, contributing to development of T2DM.

Analysis and Modelling of Non-Fourier Heat Behavior Using the Wavelet Finite Element Method.

Non-Fourier heat behavior is an important issue for film material. The phenomenon is usually observed in some laser induced thermal responses. In this paper, the non-Fourier heat conduction problems with temperature and thermal flux relaxations are investigated based on the wavelet finite element method and solved by the central difference scheme for one- and two-dimensional media. The Cattaneo-Vernotte model and the Dual-Phase-Lagging model are used for finite element formulation, and a new wavelet finite element solving formulation is proposed to address the memory requirement problem. Compared with the current methodologies for the Cattaneo-Vernotte model and the Dual-Phase-Lagging model, the present model is a direct one which describe the thermal behavior by one equation about temperature. Compared with the wavelet method proposed by Xiang et al., the developed method can be used for arbitrary shapes. In order to address the efficient computation problems for the Dual-Phase-Lagging model, a novel iteration updating methodology is also proposed. The proposed iteration algorithms on time avoids the use the global stiffness matrix, which allows the efficient calculation for title issue. Numerical calculations have been conducted in the manner of comparisons with the classical finite element method and spectral finite element method. The comparisons from accuracy, efficiency, flexibility, and applicability validate the developed method to be an effective and alternative tool for material thermal analysis.

S-DNA and RecA/RAD51-Mediated Strand Exchange in Vitro.

S-DNA (stretched DNA) is an elongated base-paired DNA conformation under high tension. Because the RecA/Rad51 family DNA recombinases form helical filaments on DNA and mediate the formation of the DNA triplex (D-loop), in which the DNA is stretched, and because the extension of these nucleoprotein filaments is similar to the extension of S-DNA, S-DNA has long been hypothesized as a possible state of DNA that participants in RecA/Rad51-mediated DNA strand exchange in homologous recombination. Such a hypothesis, however, is still lacking direct experimental studies. In this work, we have studied the polymerization and strand exchange on S-DNA mediated by Escherichia coli RecA, human Rad51, and Saccharomyces cerevisiae Rad51 by single-molecule magnetic tweezers. We report that RecA/Rad51 polymerizes faster on S-DNA than on B-DNA with the same buffer conditions. Furthermore, the RecA/Rad51-mediated DNA triplex forms faster from S-DNA than from B-DNA together with the homologous single-stranded DNA. These results provide evidence that S-DNA can interact with RecA and Rad51 and shed light on the possible functions of S-DNA.

Engineering tunable biosensors for monitoring putrescine in Escherichia coli.

Biosensors can be a powerful tool for real-time monitoring of specific small molecules and for precise control of gene expression in biological systems. Thus, biosensors have attracted much attention for monitoring increasing number of molecules. However, strategies to tune the properties of biosensors remain less explored, which might restrict their wide applicability. Here we report the development of tunable biosensors for monitoring putrescine, an important member of biological polyamines, in Escherichia coli. The native putrescine-responsive PuuR repressor protein was employed as a sensing component, and its cognate operator was installed in engineered promoters to control the expression of downstream green fluorescent protein (GFP) mut3 as a reporter protein. The engineered biosensors were specific for putrescine, and the response time could be modulated by altering growth medium of the biosensor strains. In addition, the response dynamics and detection ranges of the biosensors can be tuned at the genetic level by modulation of PuuR expression, and by manipulation of the chromosomal genes involved in putrescine biosynthesis. To demonstrate utility of the biosensors, we were able to monitor the changes of endogenous putrescine levels caused by genetic manipulations. Furthermore, a link between the excretory putrescine titer and intracellular GFP fluorescence was established for an E. coli strain that was engineered for improved putrescine biosynthesis and excretion. This study provides a strategy for engineering synthetic biosensor circuit for monitoring and tuning the dynamics in sensing putrescine, which can be generally applicable for monitoring other chemicals through taking a similar approach in circuit design.

The relationships among Muslim Uyghur and Kazakh disabled elders' life satisfaction, activity of daily living, and informal family caregiver's burden, depression, and life satisfaction in far western China: A structural equation model.

1 Hypothesis Disabled elders' activities of daily living, caregiver burden, caregiver depression, and caregivers' life satisfaction are significantly related to the life satisfaction of elderly people with disability. 2 Hypothesis There are direct and indirect effects between the life satisfaction of elders, disabled elders' activities of daily living, and family caregivers' factors. This study explored the interrelationships of disabled elders' life satisfaction and activities of daily living, caregivers' factors (burden, depression, and life satisfaction) through a structural equation model. In total, 621 dyads of disabled elders and informal family caregivers completed questionnaires during face-to-face interviews in Xinjiang Uyghur Autonomous Region from September 2013 to January 2014. Activity of daily living exerted a direct effect on life satisfaction of disabled elders and 30.4% indirect effect through caregivers' factors. Caregiver burden had a 60.0% direct effect on life satisfaction of disabled elders and a 40.0% indirect effect through the caregiver depression. Caregiver depression showed 76% direct effect on life satisfaction of disabled elders and 24% indirect effect through caregivers' life satisfaction. Direct relationships between activity of daily living and caregiver burden, caregiver burden and caregiver depression, and caregiver depression and caregivers' life satisfaction were observed. Activity of daily living had a 91.3% indirect effect on caregiver depression mediated by caregiver burden; caregiver burden had a 40.0% indirect effect on caregivers' life satisfaction mediated by caregiver depression. Results provide useful information for nurses and policymakers and shed light on the need to consider caregivers' factors in improving care recipients' life satisfaction.